Process of preparing n, n-dimethylamino alcohols



- d S P r 3,402,203 V I Patented Sept. 17, 1968 3,402,203 PROCESS OF PREPARING N,N-DIMETHYL- CH --CH OH 3HCHO AMINO ALCOHOLS I John B. Tindall, Terre Haute, Ind., assignor to Commercial Solvents Corporation N0 Drawing. Filed Nov. 19, 1964, Ser. No. 412,301

7 17 Claims. (Cl. 260-584) ABSTRACT OF THE DISCLOSURE .formic acid,

The invention relates to a process for the manufacture of N,N-dimethylamino alcohols and to a process for the conversion of, for example, dialkylamino primary and secondary alcohols to dialkylamino secondary and tertiary alcohols.

Heretofore N,N-dialkylamino alcohols such as, for example, 2-dimethylamino-2-methyl-l-propanol, have been prepared by hydrogenating an amino alcohol, e.g. 2- amino-Z-methyl-l-propano1 in the presence of an aldehyde such as formaldehyde under conditions requiring the use of substantial amounts of hydrogen and Raney nickel catalyst or by refluxing 2-amino-2-methyl-1-propanol :and formaldehyde with formic acid. Thedisadvantages ofthese prior processes are numerous. For example, when hydrogenating an'amino alcohol, largequantities of-catalyst are needed. Addition-ally, thereaction products are solutions containing'a low concentration'of the desired material which must be further concentrated, and furthermore, the reaction products are mixtures of isomers which are diflicult to separate.

This invention has as its object the preparation of N,N-dim'ethylamino alcohols by a new and improved process. This invention has as a further object the provision of a new and improved process for replacing, by methyl, each of the hydrogens on the amino nitrogen of an amino alcohol. Another object of the presCntinVention is a process whereby N,N-dimethyl-amino alcohols and isomers thereof may be selectively produced. A still further object is a process for the isomerizationof N,N- dialkylamino alcohols, i.e. for the conversion of dialkylamino primary and secondary alcohols to dialkylarnino secondary and tertiary alcohols. Another objectfis the use of available and low-priced raw materials.

The above objects are accomplished by the invention which is described herein with reference to the selective .prod c omnf .2-d m v .am -rnethy -lrp o ol a d 1-dimethylamino-Z-methyl-Z-propanol. It is to be understood, however, thattheinvention is not limited to the production of only these compounds but can be generally used for the production of N,N-dimethylamino al- '-cohols and for the isomerization of N,N-dialkylamino al- 2c'ohols.

In general, the process of ,the present invention com prises heating 2-a'mino-2-m ethyl-l-propanol and formaldehyde in proportions corresponding to a mol ratio of at least about three mols of formaldehyde for each mol of amine at a temperature and for a period of time sufficient to produce 2-dimethylamino-2-methyl-l-propanol. The net overall reaction is represented by the equation:

The reaction can, for example, be carried out in an autoclave and the amino alcohol and formaldehyde can be charged directly to the autoclave or premixed beforebeing charged to the autoclave. The components can be added to the autoclave or premixing vessel in any order.

After the reaction is completed, the temperature is lowered and the reaction product is first distilledazeotropically to remove the water produced by the reaction. Then, if the desired product is Z-dimethylamino-2-methyll-propanol, the presence of formic acid (which may be produced as a by-product) in the reaction mixture is avoided, for example, by the addition of a strong alkali to neutralize the reaction mixture and the product separated by distillation; whereas, if the desired product is 1-dimethylamino-Z-methyl-Z-propanol, the presence of formic acid or a formic acid donor in the reaction product prior to distillation is insured and the Z-dimethylamino-Z-methyl-l-propanol is converted to l-dimethylamino-2-methyl-2-propanol by heating and thereafter the desired product is separated.

In addition to formaldehyde, paraformaldehyde and other formaldehyde-releasing substances may be used in the present invention. "Also, the aldehyde may, for example, be commercially available formaldehyde which is stabilized with, for example, methanol; however, if methanol is present in the aldehyde, the methanol should be removed by distillation prior to azeotropic distillation of the water. Formaldehyde is used with the amino alcohol reaction.

Reaction temperatures suitable for the present invention are generally from about to 200 C., and preferably temperatures of from about to C. are used. Variations in temperature tend to produce mixtures of isomers of the desired product, as Well as by-products including possibly various oxazolidines, 2-monomethylamino-2-methyl-l-propanol, etc., which are diflicult to separate from the desired product. The reaction time required is dependent upon the temperature and rectants used.

Suitablereaction times are from about 1 to 30 hours and preferably 1 to 20 hours, e.g. about 4 hours with shorter reaction times being required at higher temperatures. Any desirable pressure can be used, for example, from atmos- V pheric to any safe degree, e.g. up to about 300 p.s.i.g., de-

pending upon the equipment used. Pressure is developed at higher temperatures by the evolution of CO and venting of the reaction vessel may be required.

Although toluene is the preferred material for use in the azeotropic distillation of water, any compound which does not react with amino alcohols, is capable of forming 0 an azeotrope with water, and may be fractionated from the product without adverse effects to the desired product may be used.. Such compounds include, for example, other azeotrope boiling at about 68 C., alkyls such as hexane and heptane, cycloalkyls such as cyclohexane, lower aliphatic alcohols, e.g. alkanols, such as butanol, etc.

It has been found that the reaction product of the amino of the pressure, e.g. by application of a vacuum or superatmospheric pressure as required.

The N,N-dialkylamino alcohols with which the present invention is principally concerned are the dialkylamino alcohols of the general formulae;

alcohol and formaldehyde can contain varying amounts R1 R3 R2 R3 of formic acid which is produced as a by-product of the I I I reaction. The amount of formic acid produced varies with Ill-Cf W the reaction temperature, larger amounts being produced N OH OH N at lower temperatures. The removal of formic acid prior R R to distillation to recover the product inhibits the formawherein R a 10 alk R R R d R tion of the isomer, e.g. l-dimethylamino-Z-methyl-Z-pro- 1 wet y an 4 are panel, and allows production of 2-dimethylamino-2-methdlvlduany selected from the group. consltlng of hydroger? yl-l-propanol in high yields. To be of any significant alkyl hydroxyalkyl and p mcludmg pheny1'Subs.t1' value however, the formic acid must be removed bealkyl and Phenyl'subsmuted .hydroxyalkyl t fore the autoclave product is distilled. Removal of the vimtlon 1s i concerned Wlth the producnon of formic acid may be accomplished for example by vacuum dimethylamlno alcohols of the above formulae wherein R distillation at low temperature, by azeotropic removal of Is i i i with the lsomfifnzation of dlalkylammo the Z-dimethylamino-2-methyl-l-propanol through distilco S o t e q i vgherem R lower Preferred lation with water before the final distillation, or by neu- 2 fizg fi g gfi u i i i f g g gg g q tralization of the acid with a strong base such as sodium the above g k u to 6 6 m or potassium hydroxides, carbonates, or bicarbonates. If e p 3 ar n a a strong base is used, it should be added in at least the pflmcularly lower alkyls and hydroxyauiyls' Such amount required to neutralize the formicacid present in dlalkylammo 511601101 astfor example l f the reaction product which may be determined by anbutanol P l l l alysis. It has been found that in general 0.1% by weight, l'pentanol 1'dlmethylanimo'z'penlanql 3'dlmethylammo' or more, preferably from about 0.5% to about 5%, by i i z'dlmethylammad'methymibutanol weight of the strong base based on reaction product, i.e. i lfdlmethylammo dialkylamino alcoh o1 is required. propanedro l-p enyl-Z-drmethylamrno 1 propanol, 1-

If the isomer, e.g. 1-dimethylamino-2-methy1-2-propanol .phenyL1'dlmethylammo'gproganol can be produced is the desired product, formic acid or a formic acid donor m g i ig i g fl i p 1 h 1 b such as formate esters, but not salts, is added to the auto- 6 m yfi i pnmary 3 co 0 5 :1? e clave product before distillation, and the autoclave prod- Tea 1y conver.te 0 y ammo Secon ary or e lary uct is heated for a period of time and at a temperature alcohols l dlalkyiammo .Secondary alcohols can sufficient to convert the 2-dimethylamino-Z-methyl-1-prof to dlalkylammo ternary p by the 150m pa n 01 to di m ethylamino 2 methy1 2 prOPanoL Gener erization process of the present invention. For example, ally the formic acid donor is added to the reaction mixz'fhmethylammo'l'butanol .converted to i' ture in an amount sufficient to provide in the reaction mix- 'p converted ture at least about 0.5%, and preferably about 1% by to 1'dlmethylammolz'pentanoi; Z'dImethYIammO'Z'meth' weight of formic acid based upon the product, i.e. dialkyl- 40 yi'l'propancgl to 1'dlmethylammo'z'methyl'zlprop 2111.01; amino alcohol since with amounts of formic acid below dlmethylammo'g"methyl'z'butanifl to z'dlmethylilmmoa' 0.5% the conversion is too slow to be economical. Alniethyls'buianol; to thoug h additional formic acid may be used, if desired, dlmethy1am1no'23'propanedlol;. 1'pheny1'.2'dlmethy1am1' amounts above 5% are unnecessary. No particular grade to l l P of formic acid donor is required; commercially available to f P' products are satisfactory. The length of the heating period dlbutylammo'l'propanol to 1'dlbutylammo'z'pmpanol, in the presence of formic acid required for the conversion to the isomer, 1dimethYlaminO 2 methy1 2 ProPanol In order to rllustratespecrfically the lnventlon, the folis dependent upon the particular material and the pressure lowmg example? are glfwm These PR merFly and temperature employei A convenient way of carrying for purposes of illustration and do not l1m1t the invention out this reaction comprises distilling the dimethylamino 111 any alcohol and formic acid through a fractionating column 'EXamPles LV and regulating the take off to keep the vapor temperature 2-amino-2-methyl-l-propanol (AMP) and f 1d at essentially the boiling point of the lower boiling isomer. r h d (1101-10) we introduced int a bomb a d ck d Generally, atmospheric pressure and temperatures of from for 4 hours at the temperatures noted in Table I hereinabout to 200 C., preferably from about to 170 below. The product of the bomb was dehydrated by azeo- C., and times of from about 1 to 45, preferably 1 to 20, tropic distillation with toluene and fractionated to obtain hours are suitable. Also, typically, the reaction times are the desired product Z-dimethylamino-Z methyl-l-propanol shorter with higher boiling compounds. The reaction tem- (Z-DMAM-l-P). The results are tabulated in Table I perature can be controlled to an optimum by regulation 60 hereinbelow.

I TABLE I Example No.

I II III IV v iii 3525 it; 'i til it; l t fi a aion a irifiiiiigF djlffII"III "IT neigg 129-13 res-3:2 148-5? mog'gg e e Pi i s i ifift go ling fp g 75 so 75 150 $v-i 3% Pmducts' 235 75 66 6 (a) '6 61 1 2, u l Wt. oi Reaction Prgduct, g 323 333 336 316 Percent of Original Base in Reaction Product. 86. 5 89.0 85.5 90. 0 87. 3 Percent of Original HCHO in Reaction Product. 10. 8 6.3 3. 9 3.2 2.3 a: at. .222 "a a: 1 0 11 11%)110 Content of Product, perce 0.45 v 0.38 0.31 0.40 0.32

1 Light Yellow. Yellow. 3 Light Amber. A mbcr. 5 Nearly Black.

V I axam les'vr-xvr b .;Several batches of Z-dimethylamino-2-methylrl-propanol (2-DMAM-l-tP) were prepared by first charging a 6 ratio was changed to 2:1 and takeotf continued to 75 on the top tray. Care was taken at this time to remove methanol from the system because it would prevent phase separation of toluene and water for decantation. Toluene anlileothantol-lstabitlized' forlrxnaldle tlde So t o a was then added to the kettle and a toluene-water azeoamihg zfin l eti l au 0; av? A NF; cu atedfiamogitdof rhfi trope distilled out at 82 to 86 C. and total takeoff. The autocl- Y 'p-( i lzg t i a e 6 water layer was decanted off and discarded and the toluene Sure 1 1; 02:112 1 6 8} k i Stage .S F t layer was returned to the kettle. When water removal was 150 I2: Externai 13:; ggs]: 3kg; tg heat tfig gg fiiog nearly complete, the bo1lup rate slowed and temperatures to about 1205-130 C. and thei eafter the heat of reaction 10 ig gzg fig g ii gg g i fiz i g gfi ggf fi f l gf p fi 1 1 11 The Heads cuts from previous distillation were added and 9 fi w fi 2 our 9" 1 the column was set on total reflux and the pressure with agitatlon. Steam pressure was usually vented off the Slowly lowered to m Hg u e ressure The jacket when the reactionliquid reached the C. t p u 15 toluene cut was then taken at total takeoff to 65 C top range. After about the first half hour of reaction, steam temperature was put backion the jacketto hold l50 C. In a few The reflug ratio was Set-at and heads cuts er cases where the temperature overran C. a flowof o w e taken at 100 mm. Hg to 95 C. top temperature. These cooling water was placed on the acket for a few minutes. e t d b Whe'nth'e reaction rem 'r'atur reachedth' 90-120 0 u s were assaye gas chromatograph for relatve V P e 20 DMAMP,1somer and oxazolidine contents. This assay derange pressure-m theautoclave-rose-as carbon dlOXlde I v V termined the d1s osition of heads cuts to discard r l was evolved from the reaction. When the pressure reached p ecyc e 325 PSigq it a vented back 275 P g to next distillation, or addition to finished product blends. Table II a a y o maction data In the auto 2 glhfAgelfilix ratio was then droped back to 1:1 and clave reaction mixture 3.2 lb. moles of formaldehyde were 25 product was taken out m ss'ganon added-tier e mo-le of AMP: This mixture is 292 posite cuts at 100 mm. The top temperature usually peaked pounds of 37% formaldehyde per 100 pounds-of AMR In at about 98 or 99 C. and then fell back toward the end Examples XHLXVL 32 moles HCHO per mole f as a boilup decreased. Product cuts were continued until AMP were :eharged'pms additional f maldehyd d d distillate rate decreased to nothing with full steam preson the basiseofoene mole f f r aldehyde per mole of 2- 30 sure of 120 p.s.i.g. on the reboiler. An analysis of the monomethylamino-Z-methyl-l-propanol (MMAMP). product cuts for Example XI was as follows:

. TABLE II Example No.

I VI VII VIII IX X XI XII XIII XIV XV XVI HCHO lb 314 485 2,425 647 600 7,200 20 AMP (lb s,) 1 106 825 220 198 2,376 65 3 80 67 94 7o The aqueous solution of autoclave etfiuent was charged to a .fiO0i-gallon batch kettle. Z-DMAM-l-P was recovered by fractionation of the-autoclave product in an 18inch diameter 40 plate pilot plant column. Autoclave effluent was about 8%;MeOH, 50% water, 32% Z-DMAM-l-P and the balance unreacted 0r partilly reacted raw materials and reaction Dy-products. Examples XIII-XVI using Peoria heads for-reaction raw materials contained .l'ess'water and methanol because less formaldehydewas needed per batch. This resulted from'the high Z-DMAM- l-P and MMAMP content of the Peoria heads. I

The distillation was run in the following manner: A methanol cut was taken at 1:1 reflux ratio and 'a'tmospheric pressure to 66 C. top temperature. The reflux 2-DMAM-1-P, percent 98.6

Isomer, percent 0.42 3,4,4-trimethyl oxazolidine, percent 0.18 4,4-dimethyl oxazolidine, percent 0.42 H O, percent 0.35

ColorAPHA e TABLE III.AUTOCLAVE REACTION YIELDS BASED ON SAMPLE RECOVERY Example VII VIII-X1 XII XIII XIV XV XVI r Itaw Material..." AMP AMP AMP Mixture N0 KOH in Distillation:

Perctnt 2DMAM1P. 30. 26. 1 30. 5 41. 1 61. 4 36. 5 36 1 Percent Isomer 0.7 5.4 2.7 2.2 0.2 0 3 1 Yield. Percent; 86 69.7 84. 3 76.8 86. 1 76. 0 74 1 With KOH in Distillation:

Percent 2-DMAM-1-P 32. 4 32. 6 Percent Isomer 0. 4 0. 4

Yield, Percent-.. 86. 7 900 7 Example XVII, (A-C) (A) To illustrate the conversion of Z-dimethylarninm Z-rnethyl-l-propanol (Z-DMAM-l-P) to l-dimethylamino Example XX The procedure of Examples VI-XVI is followed with the following materials to produce the products listed:

Aminoalcohol Aldehyde Product 2-amino-1-butanol Paraformaldehyde 2-dimethylamino-l-butanol. 2-um1no1-pentanol Formaldehyde. 2-dimethylamino-l-pentanol. 2-amiuo-2-methyl-1-hexanol do 2-dimethylamino-2-methyl1-hexanol.

Z-amino-Lnonanol 2-amino-1-decanol 3-amino-2-methyl-2-bnt 2-amino-1,3-propanediol Z-dimethylamino-l-nonanol. 2-dimethylamino-1-decanol. 3-dimethylamino-3-methyl-2-butan01. 2'dimethylamino-1,S-propanediol.

2-amino-l-phenyl-l-propa Formaldehydel-phenyl-Z-dimethylamino-l-propanol. 3-phenyl-2-ammo-1-butanol do 3-phenyl-2-dimethylamino-1-butanol. 2-am1no-2-hydroxymethyl-1-propanol do 2dimethylamino2-hydroxymethyl-l-propanol.

2-methyl-2-propanol (1-DMAM-2-P), a mixture of 109 g. of Z-DMAM-l-P (95.5%), 100 ml. of H 0, 1 ml. of 88% HCOOH and 100 ml. toluene was distilled through a column, freed from water, then fractionated. The fractions analyzed as follows:

Example XXI The procedure of Example XVII is followed to convert the following aminoalcohols to the isomer:

Primary or secondary alcoholConverted to, respectively-Secondary or tertiary alcohol 2-dimethylamino-l-butanol 2-dimethylamino-1-pentano 2-dimethylamino-2-methyl- 2-dimethylaminod-nonanol 2-dimethylamino-1-decanol 3-dimethylaminoQ-methyl-Z-butanol. 2-dimethylamino-1,3-propanedioL.

l-phenyl-Z-dimethylamino-1-propanol- 2-diethylarnino-1-pentanol 2-dibutylamino-l-propanol 2-diamy1amino-1-propanol 3-phenyl-Z-dimethylamino-l-butanol Z-dimethylamino-2-hydroxymethyl-l-propanol Cut No Temp. Weight 2-DMAM-1P 1-DMAM-2-P 110-115 (Toluene-discarded) 115-129 0. I 42 129-133 63 2. 2 96 133-150 15. 5 27 70 5 Residue 20. 7 86 3. 5

.Yield of 1-dimethylamino-2-methyl-2-propanol is 70%.

(B) 2-dimethylamino-1-butanol when distilled with 3 wt. percent formic acid gave a 44% conversion to l-dimethylamino-Z-butanol in eight hours. The liquid temperature remained at 168170 C. while the vapor temperature was 146-148 C.

(C) When Z-dimethylamino-l-propanol was distilled as in Example XVII (B), the conversion to l-dimethylamino- 2-propanol was 39% in 24 hours. The liquid temperature was 150 :1 at all times while the vapor temperature was held at 125-130 C.

Example XVIII Seven autoclave batches of the reaction product obtained by reacting 2-amino-2-methyl-1-propanol (AMP) with formaldehyde in accordance with the procedure of Examples VI-XVI having varying amounts of formic acid present in the reaction mixture were treated for conversion of'the 2-DMAM-1-P to its isomer. The results are tabulated below:

It is claimed:

1. A method for the production of N,N-dimethylamino alcohols consisting essentially of heating an amino alcohol represented by the formula:

wherein R R R and R are individually selected from the group consisting of hydrogen, alkyl, hydroxyalkyl and phenyl with formaldehyde in a mol ratio of at least about 3 mols of aldehyde per mol of amine at a temperature of from about to about 200 C. for a period of time sufiicient to produce the N,N-dimethylamino alcohol corresponding to said amino alcohol and thereafter separating the N,N-dimethylamino alcohol from the reaction mixture.

2. The method of claim 1 wherein said temperature from about to about 160 C.

3. The method of claim 1 wherein said N,N-dimethylamino alcohol is separated by distillation.

4. .The method of claim 1 wherein said mol ratio is from about 3.1 to 3.5 mols of formaldehyde per mol of amine.

Percent Autoclave Formic Percent Percent Batch No. Temp., 0. Acid in 2-DMAM-1-P 1-DMAM-2-P Reaction Mixture Example XIX 5. The method of claim 4 wherein said temperature is AMP and formaldehyde are reacted in accordance with the process of Examples VI-XVI and the Z-DMAM-l-P converted to l-DMAlM-Z-P without isolation by the addition of formic acid with subsequent heating.

from about 120 to about C. and said time is from about 1 to 20 hours.

6. A method for the production of N,N-dimethylamino alcohols represented by the formula:

wherein R R R and R are individually selected from the group consisting of hydrogen, alkyl, hydroxyalkyl and phenyl, consisting essentially of heating an amino alcohol represented by the formula:

wherein R R R and R have the above-designated meanings, with formaldehyde in a mol ratio of at least about 3 mols of aldehyde per mol of amine at a temperature of from about 80 to about 200 C. for a period of time sufficient to produce said N,N-dimethylamino alcohol, removing formic acid present in the reaction mixture, and thereafter separating said N,N-dimethylamino alcohol from the reaction mixture by distillation.

7. The method of claim 6 wherein the formic acid is effectively removed by neutralization thereof with a strong base.

8. The method of claim 6 wherein said amino alcohol is 2-amino-2-methy1-1-propanol and said N,N-dialkylamino alcohol is Z-dialkylamino-Z-methyl-l-propanol.

9. A method for the production of an N,N-dimethyl amino alcohol represented by the formula:

R2 R3 Raga...

OH N(CH3)2 wherein R R R and R are individually selected from the group consisting of hydrogen, alkyl, hydroxyalkyl and phenyl, consisting essentially of reacting an amino alcohol of the general formula:

wherein R R vR and R have the above meanings, adding a sufiicient amount of a formic acid donor to said reaction mixture to provide at least about 0.5% by weight formic acid in said mixture based on said compound and heating the said mixture at a temperature and for a period of time sufiicient to convert said compound to said N,N- dimethylamino alcohol.

10. The method of claim 9 wherein said formic acid is present in amounts of from about 1 to by weight based on the weight of the compound.

11. The method of claim 9 wherein said amino alcohol is 2-amino-2-methyl-l-propanol, said compound is 2di methylamino 2 methyl-l-propanol and said dimethylamino alcohol is 1-dimethylamino-2-methyl-2-propanol.

12. The method of claim 9 where the temperature and time for said reaction of the aminoalcohol and aldehyde are, respectively, from about 120 to 160 C. and from about 1 to 20 hours.

13. The method of claim 12 wherein said temperature and time for the conversion of said compound to said N,N-dimethylamino alcohol are, respectively, from about to 200 C. and from about I to 40 hours.

14. A method of converting a first dialkylamino alcohol of the general formula:

R2 R3 Rt---Rt It 611 R/ R to a second dialkylamino alcohol of the general formula:

R2 R3 Rl R4 AH It wherein R is lower alkyl and R R R and R are individually selected from the group consisting of hydrogen, alkyl, hydroxyalkyl and phenyl, comprising heating said first dialkylamino alcohol in the presence of at least about 0.5% by weight of a formic acid donor based on the weight of said first dialkylamino alcohol for a period of time and at a temperature sufficient to convert said first dialkylamino alcohol to said second dialkylamino alcohol.

15. The method of claim 14 wherein said temperature is from about 80 to 200 C. and said time is from about 40 to 1 hours.

16. The method of claim 14 wherein said temperature is from about to C. and said time is from about 20 to 1 hours.

17. In a method for the production of N,N-dialkylamino alcohols represented by the formula:

N H R R wherein R is lower alkyl and R R R and R are individually selected from the group consisting of hydrogen, alkyl, hydroxyalkyl and phenyl, comprising reacting an amino alcohol with an aldehyde and thereafter separating said N,N-dialkylamino alcohol from the resulting reaction mixture, the improvement of a method for reducing the production of isomer compounds of said dialkylamino alcohols comprising adding a sufiicient amount of a strong base to said reaction mixture prior to said separation to neutralize the formic acid present therein and thereafter separating said N,N-dialkylamino alcohol from the reaction mixture by distillation.

References Cited UNITED STATES PATENTS 3,091,640 5/1963 Seeger et a1. 260-570.6 XR

OTHER REFERENCES Eschweiler: Ber. Deut. Chem., vol. 38, pp. 880-882 (1905).

FLOYD D. HIGEL, Primary Examiner. 

